RAN_MACFA
ID RAN_MACFA Reviewed; 216 AA.
AC Q4R4M9;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=GTP-binding nuclear protein Ran;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:P62826};
DE AltName: Full=GTPase Ran;
DE AltName: Full=Ras-related nuclear protein;
GN Name=RAN; ORFNames=QccE-21074;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: GTPase involved in nucleocytoplasmic transport, participating
CC both to the import and the export from the nucleus of proteins and
CC RNAs. Switches between a cytoplasmic GDP- and a nuclear GTP-bound state
CC by nucleotide exchange and GTP hydrolysis. Nuclear import receptors
CC such as importin beta bind their substrates only in the absence of GTP-
CC bound RAN and release them upon direct interaction with GTP-bound RAN,
CC while export receptors behave in the opposite way. Thereby, RAN
CC controls cargo loading and release by transport receptors in the proper
CC compartment and ensures the directionality of the transport.
CC Interaction with RANBP1 induces a conformation change in the complex
CC formed by XPO1 and RAN that triggers the release of the nuclear export
CC signal of cargo proteins. RAN (GTP-bound form) triggers microtubule
CC assembly at mitotic chromosomes and is required for normal mitotic
CC spindle assembly and chromosome segregation. Required for normal
CC progress through mitosis. The complex with BIRC5/survivin plays a role
CC in mitotic spindle formation by serving as a physical scaffold to help
CC deliver the RAN effector molecule TPX2 to microtubules. Acts as a
CC negative regulator of the kinase activity of VRK1 and VRK2. Enhances
CC AR-mediated transactivation. {ECO:0000250|UniProtKB:P62826}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000250|UniProtKB:P62826};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P62826};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P62826};
CC Note=Mg(2+) interacts primarily with the phosphate groups of the bound
CC guanine nucleotide. {ECO:0000250|UniProtKB:P62826};
CC -!- SUBUNIT: Monomer. Interacts with RANGAP1, which promotes RAN-mediated
CC GTP hydrolysis. Interacts with KPNB1. Interaction with KPNB1 inhibits
CC RANGAP1-mediated stimulation of GTPase activity. Interacts with RCC1
CC which promotes the exchange of RAN-bound GDP by GTP. Interaction with
CC KPNB1 inhibits RCC1-mediated exchange of RAN-bound GDP by GTP.
CC Interacts (GTP-bound form) with TNPO1; the interaction is direct.
CC Interacts (GTP-bound form) with TNPO3; the interaction is direct.
CC Interacts with KPNB1 and with TNPO1; both inhibit RAN GTPase activity.
CC Interacts (via C-terminus) with RANBP1, which alleviates the inhibition
CC of RAN GTPase activity. Interacts with RANGRF, which promotes the
CC release of bound guanine nucleotide. RANGRF and RCC1 compete for an
CC overlapping binding site on RAN. Identified in a complex with KPNA2 and
CC CSE1L; interaction with RANBP1 mediates dissociation of RAN from this
CC complex. Interaction with both RANBP1 and KPNA2 promotes dissociation
CC of the complex between RAN and KPNB1. Identified in a complex composed
CC of RAN, RANGAP1 and RANBP1. Identified in a complex that contains
CC TNPO1, RAN and RANBP1. Identified in a nuclear export complex with
CC XPO1. Found in a nuclear export complex with RANBP3 and XPO1. Interacts
CC with RANBP2/NUP358. Interaction with RANBP1 or RANBP2 induces a
CC conformation change in the complex formed by XPO1 and RAN that triggers
CC the release of the nuclear export signal of cargo proteins. Component
CC of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and
CC XPO1 (By similarity). Found in a nuclear export complex with RAN, XPO5
CC and pre-miRNA (By similarity). Interacts (GTP-bound form) with XPO5 (By
CC similarity). Part of a complex consisting of RANBP9, RAN, DYRK1B and
CC COPS5. Interacts with RANBP9 and RANBP10. Interacts in its GTP-bound
CC form with BIRC5/survivin at S and M phases of the cell cycle. Interacts
CC with TERT; the interaction requires hydrogen peroxide-mediated
CC phosphorylation of TERT and transports TERT to the nucleus. Interacts
CC with MAD2L2. Interacts with VRK1 and VRK3. Interacts with VRK2 (By
CC similarity). Interacts with NEMP1 and KPNB1 (By similarity). Interacts
CC (GDP-bound form) with NUTF2; regulates RAN nuclear import. Interacts
CC with CAPG; mediates CAPG nuclear import. Interacts with NUP153.
CC Interacts with the AR N-terminal poly-Gln region; the interaction with
CC AR is inversely correlated with the poly-Gln length (By similarity).
CC Interacts with MYCBP2, which promotes RAN-mediated GTP hydrolysis (By
CC similarity). Interacts with EPG5 (By similarity).
CC {ECO:0000250|UniProtKB:P62825, ECO:0000250|UniProtKB:P62826,
CC ECO:0000250|UniProtKB:P62827}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P62826}. Nucleus
CC envelope {ECO:0000250|UniProtKB:P62826}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P62826}. Cytoplasm
CC {ECO:0000250|UniProtKB:P62826}. Melanosome
CC {ECO:0000250|UniProtKB:P62826}. Note=Predominantly nuclear during
CC interphase. Becomes dispersed throughout the cytoplasm during mitosis
CC (By similarity). Identified by mass spectrometry in melanosome
CC fractions from stage I to stage IV (By similarity).
CC {ECO:0000250|UniProtKB:P62826}.
CC -!- PTM: Acetylation by KAT5 at Lys-134 is increased during mitosis,
CC impairs RANGRF binding and enhances RCC1 binding. Acetylation at Lys-37
CC enhances the association with nuclear export components. Deacetylation
CC of Lys-37 by SIRT7 regulates the nuclear export of NF-kappa-B subunit
CC RELA/p65. {ECO:0000250|UniProtKB:P62826}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ran family.
CC {ECO:0000305}.
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DR EMBL; AB169865; BAE01946.1; -; mRNA.
DR RefSeq; NP_001271555.1; NM_001284626.1.
DR AlphaFoldDB; Q4R4M9; -.
DR SMR; Q4R4M9; -.
DR STRING; 9541.XP_005572689.1; -.
DR GeneID; 102133660; -.
DR CTD; 5901; -.
DR VEuPathDB; HostDB:ENSMFAG00000003494; -.
DR eggNOG; KOG0096; Eukaryota.
DR OMA; TIVFHRK; -.
DR OrthoDB; 1083175at2759; -.
DR Proteomes; UP000233100; Chromosome 11.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005635; C:nuclear envelope; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0046039; P:GTP metabolic process; ISS:UniProtKB.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; ISS:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; ISS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0061015; P:snRNA import into nucleus; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR002041; Ran_GTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR PANTHER; PTHR24071; PTHR24071; 1.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00627; GTPRANTC4.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51418; RAN; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cell cycle; Cell division; Cytoplasm; GTP-binding; Hydrolase;
KW Isopeptide bond; Magnesium; Metal-binding; Mitosis; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Protein transport; Reference proteome; Transport;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT CHAIN 2..216
FT /note="GTP-binding nuclear protein Ran"
FT /id="PRO_0000249773"
FT REGION 211..216
FT /note="Interaction with RANBP1"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT BINDING 18..25
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT BINDING 36..42
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT BINDING 68
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT BINDING 122..125
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT BINDING 150..152
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62825"
FT SITE 69
FT /note="Essential for GTP hydrolysis"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT MOD_RES 24
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT MOD_RES 37
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT MOD_RES 60
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT MOD_RES 71
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT MOD_RES 99
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT MOD_RES 134
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT MOD_RES 159
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT MOD_RES 159
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P62827"
FT CROSSLNK 71
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT CROSSLNK 71
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P62826"
FT CROSSLNK 152
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P62826"
SQ SEQUENCE 216 AA; 24423 MW; D5C9B7275C34BCE0 CRC64;
MAAQGEPQVQ FKLVLVGDGG TGKTTFVKRH LTGEFEKKYV ATLGVEVHPL VFHTNRGPIK
FNVWDTAGQE KFGGLRDGYY IQAQCAIIMF DVTSRVTYKN VPNWHRDLVR VCENIPIVLC
GNKVDIKDRK VKAKSIVFHR KKNLQYYDIS AKSNYNFEKP FLWLARKLIG DPNLEFVAMP
ALAPPEVVMD PALAAQYEHD LEVAQTTALP DEDDDL
